The objectives of this project are to confirm and expand the evidence for inhibition of N-Butyl-N-(4 Hydroxybutyl)-nitrosamine (OH=BNN) induced urinary bladder carcinogenesis in Fischer 344 rats with 2-Hydroxyethyl retinamide (2-HER) and to study the chronic toxicity of the retinamide. To realize these objectives, experiments are being conducted to investigate the following: 1. Assess the degree of toxicity and bioaccumulation of 2-HER anti-neoplastic and higher doses. 2. Through sequential and long-term observations, determine if 2-HER influences the biological behavior of pre-neoplastic and neoplastic lesions. 3. Compare the efficiency of 2-HER urinary bladder tumor inhibition when administered before rather than after exposure to the carcinogen, i.e., by an effect on initiation as well as on promotion or progression. 4. Determine if 2-HER affects carcinogen induced macromolecular synthesis in the urothelium at various stages in the carcinogenic process. The toxicity experiment compares the effects of lifetime feeding of @ to 5.0 mM of 2-HER/kg of diet. Body weights, food intake, toxicological, biochemical and pathological parameters will be evaluated. The carcinogenesis study includes groups of 85 rats each getting 1.5 mM 2-HER/kg of food. Sequential sacrifices with pathological examinations, including scoring of urinary bladder lesions, are done. Experiments measuring possible urothelium DNA, RNA, and protein synthesis changes will utilize 3H-thymidine, 3H-orotic acid, and 3H-leucine isotope labelling, respectively. Transplantation studies will involve retinoid versus non-retinoid syngeneic recipients.